The autoimmune thyroid diseases (AITD) are common human autoimmune dysfunctions encompassing thyroid gland over activity (Graves' disease -GD) and failure (Hashimoto's thyroiditis - HT). The AITD affect up to 10% of the population; mostly women (5:1). Because these diseases are familial, and 30% of identical sibs show concordance, our hypothesis has been that these diseases have a major genetic component. Although their inheritance pattern is complex, tools are now available to begin the search for such genes. Our recent study is involving 100 families have produced evidence of multiple loci involved in AITD. Four of the loci showed strong evidence that they affected the expression of AITD. Other loci showed some evidence for linkage but more data are necessary to confirm them. The data also revealed evidence of heterogeneity within the clinical phenotypes; in particular those patients with HT. It is now necessary to develop a larger data set for the following reasons: (1) There is genetic heterogeneity within the same disease phenotypes, (2) The analysis methods for coping with heterogeneity in small data sets are weak, (3) There is a need to subdivide the data to stratify by specific characteristics to take account of heterogeneity using clinical criteria which will lead to reduced numbers for analysis and, (4) Once we have found linkage we need to detect associations in order to identify the gene and, therefore, need a large enough sample to analyze by this method. Statistical simulations suggest that 200 families should produce more definitive data. Hence the aims of this application are (1) To collect 100 additional multiplex new families with autoimmune thyroid disease and obtain important clinical and epidemiological data as well as DNA and peripheral blood lymphocytes from probands and family members. This will bring our collection to 200 . families, (2) We will perform a first round whole genome screening on the 200 families using 400 micro satellites and (3) The whole genome screening data from the -1,000 individuals will be analyzed to determine loci with LOD scores >2.0 and the identified loci will be fine mapped with multiple additional micro satellites to narrow the regions of interest. These studies will provide more definitive data on the linked and associated loci contributing to AITD.